Radical addition of alkyl radicals

In our group, we have explored the radical addition of alkyl radicals [97] and anomeric radicals [115] to sugar enones 134 having an exo double bond (see Schemes 46 and 47). Comparison of radical and anionic 1,4-addition, shown here, yields strictly equivalent stereoselectivities. The selectivity also depends on the nature of the entering radical, and reversal of stereoselectivity is observed on going from primary alkyl radicals to the larger t-butyl radical [for analogous observations see also Ref. 116]. 

Inverse Radical Addition of Alkyl Radicals to Perfluoroolefins... 

Scheme 2.39 Radical addition of alkyl radicals to unsaturated chemical bond [218-226]...

Protonated /V-chloroalkyl amines under the influence of heat or uv light rearrange to piperidines or pyrroHdines (Hofmann-Lriffler reaction) (88). The free-radical addition of alkyl and dialkyl-/V-chloramines to olefins and acetylenes yields P-chloroalkji-, P-chloroalkenyl-, and 8-chloroalkenylamines (89). Various N-hiomo- and N-chloropolyfluoroaLkylarnines have been synthesized whose addition products to olefinic double bonds can be photolyzed to fluoroazaalkenes (90). 

The hexabutyldistannane used in this reaction is not involved in the propagation sequence but may be involved in initiation or scavenging of potential chain-termination radicals. Intermolecular additions of alkyl radicals to alkynes have also been observed. 

Michael acceptors and 1,4-addiiion of alkyl group is a normal process. The reaction mechanism is not clear, but the process via addition of alkyl radicals and subsequent elimination of NO radical is one of the possible routes. Recently, several related reactions have been reported, as shown in Eq. 4.76, Eq. 4.77, and Eq. 4.78, in which alkyl radicals are involved. The reaction of trialky Igalliiim compounds with nitrostyrene gives also a similar snbsdtiidon product fEq. 4.791. ° ... 

A similar but asymmetric variant of the reaction, involving the radical addition of alkyl iodides and trialkylboranes to chiral azirine esters derived from 8-phenyl-menthol and camphorsultam, in the presence of a Cu(i) catalyst, has subsequently been reported [64]. The diastereoselectivity of the addition is variable (0-92% de)... 

Figure 1.3 Relative rate constants for addition of alkyl radicals to fumarodinitrilc (k ) and methyl a-chloroacrylate (kz) as a function of temperature (Scheme 1.6).65...

Kim and coworkers introduced silyl radical mediated addition of alkyl radical to silyloxy enamine 76. The silyloxy enamine moiety is readily accessible from a variety of functionalities. The mechanistic concept is illustrated in the Scheme 12 and involves the addition of R radical to 76 to give the radical adduct 77 and the subsequent homolytic cleavage of N-O bond to yield the desired product 78 and a silyloxy radical 79. The latter undergoes 1,2-phenyl migration to give the silyl radical 80 that abstracts halogen from the alkyl halide to regenerate the R radical. 

Free-radical addition of alkyl halides to alkenes... 

The radicals generated in this way can initiate a variety of chain processes. Alkyl radicals can be generated from alkyl iodides.298 For example, addition of alkyl radicals to alkynes can be accomplished under these conditions. 

Esters are commonly regarded as unreactive toward addition of alkyl radicals [120]. Recently, two studies have demonstrated that this may not be true. In the first, somewhat special, example, the addition of a benzylic radical to the carbonyl group of butenolides was observed during the preparation of potential novel /3-lactam antibiotics (Scheme 29) [118]. 

The Ir11 dimer [Ir(oep)]2 (oep = octaethylporphyrin) has been prepared in low yield by photolysis of (oep)IrCH3 in C6D6.473 This preparation has been improved by Chan et al.474, as shown in Reaction Scheme 24, where TEMPO = 2,2,6,6-tetramethyl-l-piperidinyloxy, free radical. The dimer undergoes several organometallic reactions, including oxidative addition of alkyl C 11 bonds and alkene insertions.475... 

The combined influences of polar and steric effects and of the strength of the newly formed bond93 was also recognized in the reaction of a,0-unsaturated carbonyl compounds and similar electron deficient alkenes95 with organomercurials and NaBH4. For the addition of alkyl radicals to substituted styrenes, p assumed a... 

Enantioselective nitro-aldol reaction (see Section 3.3) or Michael reaction (see Section 4.4) followed by radical denitration is useful as an alternative indirect method of enantioselective 1,2- or 1,4-addition of alkyl anions (see Eq. 7.7087 and Eq. 7.7188). 

No effect of this type is manifested for the addition of alkyl radicals to the same alkenes. Evidently, the steric effect involved in the addition of trialkylsilyl radicals to 1,2-disubstituted ethylene derivatives is due to the repulsion between the carbon and silicon atom, caused by the large size of the silicon atom in the reaction center of the transition state. 

Quinones (Q) are well known as inhibitors of radical polymerization they terminate chains by the addition of alkyl radicals via the following reactions [7] ... 

I. Addition of C-Radicals to Nitrones Recently (525), the addition of alkyl radicals to chiral nitrones as a new method of asymmetrical synthesis of a-amino acids has been described. Addition of ethyl radicals to glycosyl nitrone (286) using Et3B as a source of ethyl radicals appears to proceed with a high stereo-control rate. 

Recently, the iron-promoted Barbier-type addition of alkyl halides to aromatic aldehydes has been reported (Equation (26)).326 According to the proposed mechanism, the initial step is the formation of an alkyl radical, which can be reduced to the corresponding carbanion. This carbanion nucleophile can react, while coordinated to the iron pentacarbonyl complex, with the corresponding aldehyde. This stoichiometric method is limited with respect to substrate scope and yield. The same authors have also developed the Reformatsky-type addition of cr-halosub-stituted carbonitriles to aldehydes and ketones in the presence of iron pentacarbonyl.3... 

Radical homologation. This tin pinacolate is known to generate trimethyltin radicals at 60° and appears to be superior to tributyltin hydride as a source of stannyl radicals for addition of alkyl halides to O-benzylformaldoxime (equation I).1 Iodides, bromides, and selenides can be used as radical precursors. The same... 

Scheme 33 Addition of alkyl radicals to quinones using trialkylboranes...

Brown and Suzuki have shown that treatment of trialkylboranes with ethenyl-(Scheme 42, Eq. 42a) and ethynyloxiranes (Scheme 42, Eq. 42b) in the presence of a catalytic amount of oxygen, affords the corresponding allylic or allenic alcohols. The mechanism may involve the addition of alkyl radicals to the unsaturated system leading to l-(oxiranyl)alkyl and l-(oxiranyl)alkenyl radicals followed by rapid fragmentation to give alkoxyl radicals that finally complete the chain process by reacting with the trialkylborane [104-106]. 

Sect. 3.2). However, this approach is limited to the few trialkylboranes that are easily available and cheap since only one of the three alkyl group is transferred. By using a triethylborane as a chain transfer reagent, the reaction could be extended to alkyl iodides as radical precursors. Bertrand [94,114] and Naito [95,97] reported both the use of triethylborane for the tin-free addition of alkyl iodides to imines. A typical example for a tentative of asymmetric addition to a glyoxylate imine is depicted in Scheme 50 (Eq. 50a). More recently additions to isatin imines were reported (Eq. 50b) as well as addition to 2H-aziridine-3-carboxylates by Lemos [100] and Somfai [101] (Eq. 50c). 

Table 11.3 Rate constants and activation parameters for additions of alkyl radicals to propadiene (la) [27],...

Allenylcobaloximes, e.g. 26, react with bromotrichloromethane, carbon tetrachloride, trichloroacetonitrile, methyl trichloroacetate and bromoform to afford functionalized terminal alkynes in synthetically useful yields (Scheme 11.10). The nature of the products formed in this transformation points to a y-specific attack of polyhaloethyl radicals to the allenyl group, with either a concerted or a stepwise formation of coba-loxime(II) 27 and the substituted alkyne [62, 63]. Cobalt(II) radical 27 abstracts a bromine atom (from BrCCl3) or a chlorine atom (e.g. from C13CCN), which leads to a regeneration of the chain-carrying radical. It is worth mentioning that the reverse reaction, i.e. the addition of alkyl radicals to stannylmethyl-substituted alkynes, has been applied in the synthesis of, e.g., allenyl-substituted thymidine derivatives [64],... 

The oxidative addition of alkyl halides can proceed in different ways, although the result is usually atrans addition independent of the mechanism. In certain cases the reaction proceeds as an SN2 reaction as in organic chemistry. That is to say that the electron-rich metal nucleophile attacks the carbon atom of the alkyl halide, the halide being the leaving group. This process leads to inversion of the stereochemistry of the carbon atom (only when the carbon atom is asymmetric can this be observed). There are also examples in which racemisation occurs. This has been explained on the basis of a radical chain... 

The addition of alkyl halides to aromatic anion radicals, generated by alkalimetal reduction in ethereal solvents, was already known in the 1950s [201] and was reviewed by Garst in 1971 [202]. The first electrochemical analogue was observed by Lund etal. [203]. These authors cathodically reduced hydrocarbons such as naphthalene, anthracene, stilbene [145, 146], and pery-lene [147-150] in the presence of alkyl halides and isolated hydrogenated and alkylated products. Similar reactions are observed when the halides are replaced by ammonium or sulfonium [204]. 

This approach involves additions of alkyl radicals to C=N bonds and snbseqnent fi-expulsion of the phenylsulfonyl group (as a radical) which react with bis(trialkyl)tin to propagate a chain. The phenylsulfonyl group lowers the energy of the LUMO of the radical acceptor, increasing the rate of addition of alkyl radicals . 

For example, addition of alkyl radicals to alkynes can be accomplished under these conditions. 

The additions of alkyl or aryl silyl chlorides to 1 -ethoxycarbonyl- 1H-azepine in HMPA solution in the presence of magnesium proceed via anion radicals to yield trans adducts... 

Processes following the mechanism described in Eq. (11) are observed for the addition of alkyl (29) and substituted alkyl (26) radicals to aromatic ligands followed by the reduction of the central cation and proton loss from the aromatic ring. In principle the central cation could also be oxidized by its radical-ligand. However, such reactions are not known. 

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